Study On The Therapeutic Effect And Mechanism Of Fangji Huangqi Decoction On Primary Nephrotic Syndrome Based On Meta-analysis And Network Pharmacology

Study one : Systematic Review of Fangji Huangqi Decoction in the treatment of Primary Nephrotic SyndromeObjective: To evaluate the clinical efficacy and safety of Fangji Huangqi Decoction in the treatment of Primary Nephrotic Syndrome(PNS).Methods: Embase、The Cochrane Library、Pub Med、CNKI、CBM、Wanfang and VIP databases were searched for all published randomized controlled trials on the treatment of PNS with Fangji Huangqi Decoction from the establishment of the databases to January 2,2021.After the two researchers screened the literature,extracted the data and assessed the risk of bias independently,the R language software was used for meta-analysis.Results: A total of 12 studies were included,including 491 cases in the experimental group and 490 cases in the control group.The results of metaanalysis showed that the experimental group was better than the control group in increasing clinical total effective rate(OR=2.96,95%CI[2.06,4.24],P<0.0001)、serum albumin level(SMD=0.86,95%CI[0.72,1.01],P<0.0001)、prothrombin time(SMD=1.36,95%CI[1.15,1.58],P<0.0001)、IL-10(SMD=1.21,95%CI[0.92,1.50],P<0.0001),and decreasing the quantity of 24 h urinary protein(SMD=-1.18,95%CI[-1.50,-0.87],P<0.0001)、total cholesterol(SMD=-0.85,95%CI[-1.33,-0.38],P=0.0005<0.05)、triglyceride(SMD=-0.56,95%CI[-0.84,-0.28],P<0.0001)、TNF-α(SMD=-1.37,95%CI[-2.61,-0.13],P=0.0307<0.05)、IL-6(SMD=-1.14,95%CI[-1.42,-0.87],P<0.0001)、IL-8(SMD=-1.41,95%CI[-1.85,-0.97],P<0.0001).But there was no significant difference in decreasing serum creatinine(SMD=-0.01,95%CI[-0.21,0.20],P=0.9255>0.05)、Platelet count(SMD=0.02,95%CI[-0.18,0.21],P=0.8682>0.05)between the two groups.In terms of safety,there were no serious adverse reactions in the study,and the reported adverse reactions were mainly concentric obesity、acne、blurred vision and leukocytosis,and the occurrence of hormone side effects in the experimental group was significantly less than that in the control group.Conclusion: Fangji Huangqi Decoction for the treatment of PNS can improve the clinical efficacy and the safety is relatively good.Due to limited quantity of the included studies,more high quality studies are required to verity the conclusion mentioned above.Study two:Study on the Mechanism of Fangji Huangqi Decoction in the treatment of PNS based on Network PharmacologyObjective: To explore the mechanism of Fangji Huangqi Decoction in the treatment of Primary Nephrotic Syndrome by Network Pharmacology method.Methods: The active components of Fangji Huangqi Decoction were collected and screened through the TCMSP,and the human target proteins corresponding to the active components were searched in the TCMSP.Uniprot and Swiss Target Prediction matched the corresponding genes of target proteins.The disease targets of PNS were obtained from Gene Cards and OMIM.Weishengxin was used to construct the Venn diagram to obtain the key targets of Fangji Huangqi Decoction in the treatment of PNS,and the protein interaction network of key proteins was obtained according to the STRING.DAVID was used to carry out GO and KEGG analysis for the key targets,and the bubble diagram of enrichment results was made by using Weisenxin platform.Cytoscape 3.7.2 was used for visualization research and network topology analysis.And the molecular docking scores were obtained by using PDB and Pub Chem database.Results: 105 active ingredients were screened out,corresponding to 376 potential targets,including 1413 targets of PNS.There were 109 common targets of herbs and diseases.The network diagram of herb-component-targetpathway showed that quercetin、kaempferol、Tetraneurin A、7,2’-dihydroxy-3’,4’-dimethoxy isoflavane were the key components of Fangji Huangqi Decoction in the treatment of PNS.PTGS2、ESR1、AR and PPARG were the key targets of this prescription in the treatment of PNS.A total of 431 items were obtained by GO analysis,340 of which were obtained by BP,involving positive regulation of RNA polymerase II promoter transcription、negative regulation of apoptosis process、drug response,etc.In CC,40 items were enriched,including cytoplasm、extracellular space and extracellular region.51 items were obtained from MF,involving protein binding、ATM binding,etc.A total of 102 pathways were enriched and analyzed,including PI3K-Akt signaling pathway,MAPK signaling pathway and TLRS signaling pathway.Molecular docking showed that quercetin had good binding ability with TNF,MAPK3 had good binding ability with isorhamnetin,and IL-6 had good binding ability with isorhamnetin.Conclusion: From the perspective of network pharmacology,the overall regulation characteristics of Fangji Huangqi Decoction with multiple components、multiple targets and multiple pathways are clarified,and the material basis and mechanism of action of Fangji Huangqi Decoction in the treatment of PNS are preliminary revealed,providing ideas and basis for subsequent studies.